Programmable autotitrating of electrical parameters of implantable medical device

ABSTRACT

We report a method of automatically titrating an electrical therapy administered to a patient by an implanted medical device to a target dosage, comprising programming the medical device with a programmed electrical therapy comprising a first target value for a first therapy parameter; programming at least one titration parameter for automatically adjusting the first therapy parameter from a first value to the first target value over a titration time period initiating the electrical therapy, wherein the first therapy parameter comprises said first value; and automatically titrating the electrical therapy by making a plurality of adjustments to the value of the first therapy parameter, whereby the first electrical therapy parameter is changed from the first value to the first target value according to a titration function. We also report a medical device system configured to implement the method.

The present application is a continuation patent application whichclaims the benefit of and priority to U.S. patent application Ser. No.14/203,394, entitled “Programmable Autotitrating of ElectricalParameters of Implantable Medical Device”, filed on Mar. 10, 2014 whichclaims the benefit under 35 U.S.C. §119(e) of prior-filed provisionalapplication 61/799,046, filed Mar. 15, 2013, the disclosures of each arehereby incorporated by reference herein.

FIELD OF THE INVENTION

This disclosure relates to medical device systems and methods capable ofautomated titration of an electrical therapy provided by an implantablemedical device (IMD) from a non-therapeutic to a therapeutic dosage.Automated therapy titration as proposed herein may facilitate reachingtarget dosage levels for electrical therapies provided by IMDs morerapidly, efficiently and cost-effectively than conventional manualprogramming adjustments that require multiple medical office visits.

SUMMARY OF THE INVENTION

In some embodiments, the present disclosure relates to a method ofautomatically titrating an electrical therapy administered to a patientby an implanted medical device to a target dosage, comprising:programming the medical device with an electrical therapy, wherein theprogrammed electrical therapy comprises a first target value for a firstelectrical therapy parameter defining the electrical therapy;programming at least one titration parameter for automatically adjustingthe first electrical therapy parameter from a first value to the firsttarget value over a titration time period of at least two days, whereinthe at least one titration parameter is selected from the titration timeperiod, a titration step interval, and a titration step magnitude;initiating the electrical therapy, wherein the first electrical therapyparameter comprises said first value; and automatically titrating theelectrical therapy by making a plurality of adjustments to the value ofthe first electrical therapy parameter, whereby the first electricaltherapy parameter is changed from the first value to the first targetvalue according to a titration function.

In some embodiments, the present disclosure relates to a method ofautomatically titrating an electrical therapy administered to a patientby an implanted medical device to a target dosage, comprising:programming the medical device with an electrical therapy, whereinprogramming comprises providing a first target value for a firstelectrical therapy parameter characterizing the electrical therapy;programming at least one titration parameter for automatically adjustingthe first electrical therapy parameter from a first value to the firsttarget value over a titration time of at least five days, wherein the atleast one titration parameter is selected from the titration timeperiod, a titration step interval, and a titration step magnitude;initiating the electrical therapy, wherein the first electrical therapyparameter comprises said first value; automatically titrating theelectrical therapy by making a plurality of adjustments to the value ofthe at least a first electrical therapy parameter, whereby the firstelectrical therapy parameter is changed from the first value to thefirst target value according to a first titration function; receiving abody signal after at least one of said plurality of adjustments to thevalue of the first electrical therapy parameter; determining whetherthere is an adverse effect associated with the at least one of saidplurality of adjustments, based upon said body signal; returning thevalue of said first electrical therapy parameter to a prior value toprovide a prior electrical therapy program, in response to determiningthat there is an adverse effect associated with said at least one ofsaid plurality of adjustments; and providing said prior electricaltherapy program to said patient. In one embodiment, the adverse effectis selected from discomfort, pain, dyspnea, voice alteration, increasedheart rate, and decreased heart rate.

In some embodiments, the present disclosure relates to a medical devicesystem for providing an electrical therapy, comprising: a programmer forprogramming an implantable medical device with an electrical therapy,wherein the programmer enables a user to program into the medical devicea first value for a first electrical therapy parameter characterizingthe electrical therapy, a first target value for the first electricaltherapy parameter, and at least one titration parameter forautomatically adjusting the first electrical therapy parameter from afirst value to the first target value over a titration time period of atleast two days, wherein the at least one titration parameter is selectedfrom the titration time period, a titration step interval, and atitration step magnitude; an electrode configured to deliver anelectrical therapy characterized by a plurality of parameters to apatient; and an implantable medical device, comprising: an electricaltherapy module to provide the electrical therapy to the patient usingsaid electrode; and a therapy titration module configured toautomatically titrate the electrical therapy by making a plurality ofadjustments to the value of the first electrical therapy parameter,whereby the first electrical therapy parameter is changed from the firstvalue to the first target value according to a titration function. Inone embodiment, the implantable medical device may comprise a body datamodule capable of receiving a body signal from the patient, a feedbackmodule configured to provide feedback data to the therapy titrationmodule, wherein the feedback data is based upon one of said body dataand a manual input from the patient or a caregiver, and wherein thetherapy titration module comprises a dynamic adjustment unit configureto return the value of the first electrical therapy parameter to aprevious value after at least a first adjustment, based on said feedbackdata.

In some embodiments, the present disclosure relates to a non-transitorycomputer readable program storage unit encoded with instructions that,when executed by a computer, perform a method as described above.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure may be understood by reference to the followingdescription taken in conjunction with the accompanying drawings, inwhich like reference numerals identify like elements, and in which:

FIG. 1 shows a schematic diagram of a medical device system, inaccordance with some embodiments of the present disclosure;

FIG. 2 shows a schematic diagram of data acquisition components of amedical device system, in accordance with some embodiments of thepresent disclosure;

FIG. 3 shows a schematic diagram of a therapy titration module,according to some embodiments of the present disclosure;

FIG. 4 shows a schematic diagram of a dynamic adjustment unit, accordingto some embodiments of the present disclosure;

FIG. 5 shows an example of a titration comprising a series of increasingadjustments to a first electrical parameter from a first value to afirst target value, according to some embodiments of the presentdisclosure;

FIG. 6 shows examples of a titration of a first electrical parameterinvolving a dynamic adjustment to a programmed titration, according tosome embodiments of the present disclosure;

FIG. 7 shows a flowchart depiction of a method, according to someembodiments of the present disclosure;

FIG. 8 shows a flowchart depiction of a method, according to someembodiments of the present disclosure;

FIG. 9 shows a flowchart depiction of a method for performing atitration process, according to some embodiments of the presentdisclosure;

FIG. 10 shows a flowchart depiction of a method for implementing atitration interrupt and/or a multi-titration process, according to someembodiments of the present disclosure;

FIG. 11 shows exemplary titration functions for two parameters,according to some embodiments of the present disclosure; and

FIG. 12 shows an exemplary titration function, according to someembodiments of the present disclosure.

While the disclosure is susceptible to various modifications andalternative forms, specific embodiments thereof have been shown by wayof example in the drawings and are herein described in detail. Thedescription herein of specific embodiments is not intended to limit thedisclosure to the particular forms disclosed, but on the contrary, theintention is to cover all modifications, equivalents, and alternativesfalling within the spirit and scope of the disclosure as defined by theappended claims.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

Illustrative embodiments of the disclosure are described herein. Forclarity, not all features of an actual implementation are described. Inthe development of any actual embodiment, numerousimplementation-specific decisions must be made to achievedesign-specific goals, which will vary from one implementation toanother. Such a development effort, while possibly complex andtime-consuming, would nevertheless be a routine undertaking for personsof ordinary skill in the art having the benefit of this disclosure.

More information regarding automated assessments of disease states,comorbidities, and the like may be found in other patent applicationsassigned to Flint Hills Scientific, LLC or Cyberonics, Inc., such as,U.S. Ser. No. 12/816,348, filed Jun. 15, 2010; and U.S. Ser. No.12/816,357, filed Jun. 15, 2010. Each of the patent applicationsidentified in this paragraph is hereby incorporated herein by reference.

More information regarding automated assessments of therapies may befound in other patent applications assigned to Flint Hills Scientific,LLC or Cyberonics, Inc., such as, U.S. Ser. No. 12/729,093, filed Mar.22, 2010; U.S. Ser. No. 13/280,178, filed Oct. 24, 2011; U.S. Ser. No.13/308,913, filed Dec. 1, 2011; and U.S. Ser. No. 13/472,365, filed May15, 2012. Each of the patent applications identified in this paragraphis hereby incorporated herein by reference.

More information regarding the detection of abnormal brain activity,such as seizures, identifying brain locations susceptible to spread ofthe abnormal brain activity, and treating the susceptible brainlocations may be found in other patent applications assigned to FlintHills Scientific, L.L.C., or Cyberonics, Inc., such as, U.S. Ser. No.13/449,166, filed Apr. 17, 2012. Any patent application identified inthis paragraph is hereby incorporated herein by reference.

More information regarding the detection of brain or body activity usingsensors implanted in proximity to the base of the skull may be found inother patent applications assigned to Flint Hills Scientific, L.L.C., orCyberonics, Inc., such as, U.S. Ser. No. 13/678,339, filed Nov. 15,2012. Any patent application identified in this paragraph is herebyincorporated herein by reference.

Over the past several decades, medical devices providing electricaltherapies to treat a number of medical conditions have been developedand approved. Examples of these therapies include pacing anddefibrillation of the heart, electrical stimulation of the spinal cordto treat intractable pain, and stimulation of the vagus nerve to treatepilepsy and depression, among others. In many cases, the patient mustbe gradually acclimated to the exogenous electrical therapy, and thetherapy is gradually increased from a very low dosage to a higher,therapeutically-effective dosage. Heretofore, this process has beenperformed manually. For example, an epilepsy patient being treated withvagus nerve stimulation may initially be provided with no stimulationfor the two weeks following implantation of the device to allow thesurgical incision and trauma to heal, after which the physician (orother healthcare provider) may manually program the device to provide arelative low dosage of pulsed electrical therapy, characterized by acurrent magnitude of 0.1 milliamps (mA)), a pulse width of 0.25milliseconds, a pulse frequency of 30 Hz, an on-time of 30 seconds, andan off-time of 300 seconds. This initial therapy dosage level may be toolow to provide a therapeutic benefit to the patient. Accordingly, thephysician may thereafter manually reprogram the patient every 2-4 weeks,to gradually increase the current magnitude in a number of steps toreach a therapeutically-effective, safe, and tolerable dosage level,e.g., from 0.1 mA to 0.5 mA, then to 0.75 mA, 1.0 mA, 1.25 mA, 1.5 mA,1.75 mA, and finally to 2.0 mA. Such adjustments, referred to herein astherapy titration as the electrical therapy is gradually increased totherapeutically-effective dosage levels, require the patient to makeadditional office visits at significant cost (in money and time) to boththe patient and the treating healthcare provider. The manual titrationprocess may in many cases delay the patient receiving a therapeuticbenefit for weeks or months.

Embodiments disclosed herein provide for programming a medical device toimplement an electrical therapy following implantation of the device,and to automatically titrate at least one parameter defining theelectrical therapy from a first value to a target value. Byautomatically titrating one or more parameters of the electricaltherapy, the patient may be more effectively, more quickly, and morecost-effectively acclimated to the therapy, and may be titrated to atherapeutically-effective dosage of the electrical therapy faster andwith less pain and discomfort. The titration may involve increasing ordecreasing electrical therapy parameters, and may comprise adjusting oneor more parameters (e.g., current (or voltage) amplitude, frequency,pulse width, on-time, off-time, and/or duty cycle) defining the therapyby incremental changes from the first value to the target value. Theadjustments to the one or more parameters may be periodic, aperiodic, orcontingent. In one embodiment, contingent adjustment refers to anadjustment that is automatically initiated, but which requires a user torespond to a prompt before the adjustment is implemented in the therapy.In one embodiment, changes may be manual or automated or in response toinput from a person. In some embodiments, two or more parameters may beautomatically titrated from respective first values to respective targetvalues. In some embodiments, undesirable side effects may be detectedand used to return one or more automatically titrated parameters to aprior value before resuming the titration to the target value. By usingside effects (such as pain, discomfort, or changes in one or more bodyindices such as heart rate) to indicate a lack of tolerance and/orsafety of a particular titration step, titration may be automaticallyadjusted to rapidly, safely and comfortably titrate the patient totherapeutically- effective, tolerable, and safe therapy dosage levels.

In some embodiments, the medical device may be programmed to establish afirst target value for a first electrical therapy parameter. The firstelectrical therapy parameter may be one or more of the previously notedparameters defining or characterizing the electrical therapy. In someembodiments, the medical device may be programmed to establish a firsttarget value for more than a first electrical therapy parameter, e.g.,the device may be programmed to establish first values and/or targetvalues for a first, a second, a third, and an nth electrical therapyparameter. The automated titration of multiple parameters may besequential, simultaneous, and/or partially overlapping, and may betailored to address one or more of efficacy, safety, and tolerability,which may be separately impacted by changes associated with each of oneor more of the individual parameters.

Embodiments of the invention also involve programming at least onetitration parameter for automatically adjusting the first (and/orsecond, third, etc.) electrical therapy parameter from the first valueto the target value. The titration parameter may be selected from atitration time period, a titration step interval, a titration stepmagnitude, and/or a titration rate. The titration time period is thetime period in which an electrical parameter is to be titrated from theinitial value to the target value, e.g., 2 weeks. In some embodiments,different titration time periods may be set for each of a plurality ofparameters characterizing the electrical signal, e.g., the current maybe titrated to the target value over a period of 2 weeks, while thepulse amplitude may be titrated to the target value over one week. Thetitration step interval is a time interval at which at least onetitration adjustment step is made. In some embodiments, all of thetitration steps are made at the same titration step interval, while inother embodiments, only the initial titration step interval is provided,and subsequent step intervals are determined based upon a titrationfunction describing how the titration is to occur (e.g., uniformly ornon-uniformly). The titration step magnitude is the magnitude of thechange made to at least one adjustment of an electrical parameter. Forexample, current adjustments may be made with a titration step magnitudeof 0.1 mA, with each new automatic current adjustment comprising a 0.1mA increase over the prior value. In some embodiments, titration stepmagnitudes may be specified for a plurality of electrical parameters(e.g., a current titration step magnitude of 0.1 mA, and a pulse widthstep magnitude of 0.05 msec). In some embodiments, all of the titrationsteps for a given electrical parameter are made at the same titrationstep magnitude, while in other embodiments, only the initial titrationstep interval is provided, and subsequent step intervals are determinedbased upon a titration function describing how the titration is to occur(e.g., uniformly or non-uniformly). In one embodiment, the automatedtitration process may occur at various different scales as a function oftitration rate. By way of a first example, the rate at which the targetvalue is reached or approached may be equivalent or comparable to thetitration step magnitude divided by the titration time interval. By wayof a second example, the rate at which a parameter is changed at a stepof the titration.

The titration adjustments may be made according to a titration functiondescribing how the titration steps are to be implemented. In oneembodiment, the titration function may be a linear stepwise function inwhich uniform titration step magnitude changes are made at uniformtitration step intervals. In other embodiments, the titration functionmay be implemented as a non-linear stepwise function, a stepwiseapproximation of a polynomial, a continuous function, or a mixedstepwise and continuous function. In an example of a non-linearfunction, one or more of the titration step interval and the titrationstep magnitude may be non-linear, and may be, for example, a parabolicor higher-order polynomial.

Non-limiting examples of various titration functions are shown in FIGS.11-12. FIG. 11 shows that various parameters may vary according todifferent functions, e.g., for the functions shown in solid lines, thecurrent (in mA) may have a convex shape over the course of thetitration, and the frequency (in Hz) may have a concave shape. Foranother example, for the functions shown in dashed lines, both currentand frequency may have the same general shape (e.g., concave) over thecourse of titration, but one may reach a final value faster than theother. FIG. 12 shows an example of a parabolic function, e.g., y=−x² forx=[−5, 0].

In some embodiments, a titration function may be self-similar or fractal(i.e., each step may have the same shape as the overall function). Also,although FIGS. 11-12 show smooth parabolic functions, a parabola (orother smooth shape) may be approximated by a series of relatively smallsteps. As the person of ordinary skill in the art, having the benefit ofthe present disclosure, will understand, other functions than thoseshown in FIGS. 11-12 may be used.

The titration function may be programmably selected by a healthcareprovider or may be a predetermined function such as a linear function.In some embodiments, the titration function may further be influenced byadditional factors such as the patient's age, health status, gender, theseverity of the disorder being treated (e.g., seizure type, frequencyand severity in patients with epilepsy), the patient's tolerance toadverse events, the patient's tolerance to pain, among other relevantfactors.

In some embodiments, the titration function may be interrupted ormodified by the occurrence of one or more events, such as one or moreside effects, patient tolerance, patient safety, or patient diseasestate, among others. For example, the titration function as initiallyprogrammed may be automatically adjusted to accelerate, slow down, ortemporarily suspend or reverse the titration process based upon one ormore body signal(s). The one or more body signals may be analyzed by themedical device and an automated adjustment of the titration process maybe performed by, e.g., lowering a parameter value that results inundesired side effects such as discomfort, pain, respiratory effects(e.g., dyspnea), voice alteration, changes in heart rate, etc., to allowthe patient additional time to accommodate to the previous stimulationdosage before resuming the titration process. In addition, feedback fromexternal sources, e.g., manual input by the patient or a caregiver may,also be used to reverse, slow down, or accelerate the titrating of thetherapy.

The titration of the therapy may be implemented by initiating theelectrical therapy with the one or more parameters to be titrated set attheir respective initial values. The therapy may thereafter be titratedby automatically adjusting the one or more electrical therapy parametersbased upon the programmed one or more titration parameters (e.g., thetitration time period, titration step period, titration step magnitude,and/or titration rate) and the titration function.

As an example, a health care provider may program a medical device toprovide an electrical therapy in which a first parameter such aselectrical pulse current increases from an initial value of 0 mA to atarget value of 2.0 mA. The therapy may be automatically titrated fromthe initial value to the target value based on the titration time periodaccording to the titration function. In one embodiment, various stepsbetween the initial value and the target value may be made such that thetitration process causes the therapy signal to have a specific value ateach of these intermediate steps until the target value is achieved.That is, the automatic titration feature may “ramp up” a parameterdefining the electrical therapy by increasing the parameter in smallincrements over a programmed titration time period. In a particularembodiment, the incremental increase may be implemented once each dayover a programmed time period selected from one day to 60 days, and mayinclude two days, three days, four days, five days, one week, ten days,two weeks, three weeks, four weeks, or any other period from 2-60 days.In one embodiment, titration may be adjusted in view of one or more ofpatient input, body signals, or brain evoked responses.

In some embodiments, a user may not need to explicitly program atitration time period. Instead, the user may program a titration stepmagnitude and a titration step interval. According to such embodiments,the electrical therapy is initiated with the therapy parameter at afirst value, and the value is iteratively increased by the titrationstep magnitude after the lapse of each titration step interval. Forexample, an electrical therapy used to provide vagus nerve stimulationtherapy to a patient may be increased by 0.1 mA (or other titration stepmagnitude) each day (or other titration step interval) until the targetvalue is reached. The patient, physician or healthcare provider may besent a message when the target dosage is reached according to someembodiments.

In other embodiments, the titration of the therapy may be automaticallyor manually altered. For example, in some embodiments, body data fromthe patient may be used to evaluate one or more effects of the automatictherapy titration. Based on the one or more effects of the therapy, thetitration of the therapy may be altered. In another embodiment, ifefficacy is detected (as determined, e.g., from body data) during thetitration process, then further titrating of the therapy may besuspended. Alternatively, if side effects of the therapy are found, thetitration may be suspended or reversed until further interaction with ahealthcare provider. In some embodiments, the titration process may bereversed upon a first detection of a side effect, and after resuming thetitration process, detection of a second or a third side effect mayresult in suspension of further automatic titration of the electricaltherapy until the patient's physician programs the medical device toresume the titration, in which case an alert may be sent to thephysician or other caregiver. In a further embodiment, if no adverseeffects of the therapy are noted, the titration of the therapy may beaccelerated to reach the target value sooner than a programmed titrationtime period. The adjustment of the titrating process may be an automatediterative process, wherein adjustments to the titrating steps may bealtered based upon body data analysis during each delivery of therapy.

FIG. 1 shows a stylized block diagram representation of a medical devicesystem, according to some embodiments of the present disclosure. Themedical device system 50 may comprise a medical device 100, electrode(s)212, lead(s) 211 coupling the electrode(s) 212 to the medical device100, sensor(s) 214, and lead(s) 213 coupling the sensor(s) 214 to themedical device 100. The electrode(s) 212 may be configured to deliver anelectrical therapy defined by a plurality of parameters to a patient.The sensor(s) 214 may be configured to collect body data relating to anybody data stream of the patient, which may include as non-limitingexamples one or more of the patient's cardiac signal (e.g., heart rate,heart rate variability), respiratory signal (e.g., respiratory rate, endtidal volume, respiratory rate variability), blood oxygen saturation,blood oxygen saturation variability, discomfort level, gastro-intestinalactivity, shortness of breath, or vocal cord function. The medicaldevice system 50 includes a programmer 250 which may be used to programthe medical device 100, which in some embodiments is an implantablemedical device (IMD), a partially implantable medical device, or aportable external medical device with one or more parameterscharacterizing the electrical therapy and one or more titrationparameters to automatically titrate the one or more parameters from afirst value to a target value. In some embodiments, a patient (manual)input device 216 may be coupled to the medical device 100 by lead(s) 215or by a wireless coupling (not shown), and may be used to provide aninput (which may be a manual input or an automatic input from, e.g., anaccelerometer other sensing device incorporated in the patient inputdevice 216) from the patient.

Various components of the medical device 100, such as controller 120,processor 115, memory 117, power supply 130, and communication unit 140have been described in other patent applications assigned to Flint HillsScientific, LLC or Cyberonics, Inc., such as, U.S. Ser. No. 12/770,562,filed Apr. 29, 2010; U.S. Ser. No. 12/771,727, filed Apr. 30, 2010; U.S.Ser. No. 12/771,783, filed Apr. 30, 2010; U.S. Ser. No. 12/884,051,filed Sep. 16, 2010; U.S. Ser. No. 13/554,367, filed Jul. 20, 2012; U.S.Ser. No. 13/554,694, filed Jul. 20, 2012; U.S. Ser. No. 13/559,116,filed Jul. 26, 2012; and U.S. Ser. No. 13/598,339, filed Aug. 29, 2012;U.S. Ser. No. 12/896,525, filed Oct. 1, 2010, now U.S. Pat. No.8,337,404, issued Dec. 25, 2012; U.S. Ser. No. 13/098,262, filed Apr.29, 2011; U.S. Ser. No. 13/288,886, filed Nov. 3, 2011; U.S. Ser. No.13/554,367, filed Jul. 20, 2012; U.S. Ser. No. 13/554,694, filed Jul.20, 2012; U.S. Ser. No. 13/559,116, filed Jul. 26, 2012; and U.S. Ser.No. 13/598,339, filed Aug. 29, 2012. Each of the patent applicationsidentified in this paragraph is hereby incorporated herein by reference.

The medical device 100 may comprise an electrical therapy module 150 togenerate an electrical therapy signal that may be provided as anelectrical therapy to a target body structure such as a cranial nerve orbrain tissue via electrodes 212. The electrical therapy signal may becharacterized by a plurality of parameters, e.g., an amplitude, a pulsewidth, a pulse frequency, a signal on-time, or a signal off-time, amongothers. The electrical therapy module 150 may be configured to deliveran electrical therapy signal having a low initial or first value of oneor more parameters upon initiation of the treatment regimen. Thetreatment regimen may be initiated after implantation of electrode(s)212, medical device 100, or other components of the medical devicesystem 50. Alternatively or in addition, the therapy may be initiated aspart of a “reboot” or “reset” of a previously suspended therapy. In oneembodiment, the electrical therapy signal may be programmed along withone or more titration parameters to titrate an electrical currentsetting for electrical pulses applied to a target structure from a firstvalue (e.g., 0 mA or 0.1 mA) to a target value for providing therapy(e.g., 2.5 mA).

The treatment regimen may be configured to treat epilepsy, depression,pain, congestive heart failure, traumatic brain injury, or obesity,among other ailments known to persons of skill in the art to be amenableto treatment by electrical therapy of the body, e.g., of neuralstructures, e.g., of the brain, spinal cord, or a cranial nerve, e.g.,the vagus nerve.

The medical device 100 may also comprise a body data module 170. Thebody data module 170 is capable of acquiring signal(s) relating to apatient's body data, processing and analyzing the signals to assess theeffects (beneficial or deleterious) of the therapy on the patient. Thebody data module 170 may also be configured to determine one of a timeseries of body data values or body index values based upon the timeseries. Such a time series of body index values may comprise at leastone of an instantaneous heart rate (HR), a heart rate variability (HRV),an instantaneous respiratory rate (RR), an instantaneous blood pressure(BP), an instantaneous blood oxygen saturation (O2S) value, a bloodoxygen saturation variability, or vocal cord function, among others.Body data module 170 is shown in FIG. 2 and accompanying descriptionbelow.

In one embodiment, the body data module 170 may comprise an evokedresponse unit 172. The evoked response unit 172 may be configured toapply a signal to a body tissue and determine what response, if any, isevoked in the tissue by the signal. For example, the evoked responseunit 172 may comprise a stimulator 174 configured to apply a signalexpected to evoke a response, and an interpreter 176 configured todetermine what response, if any, was evoked by the signal.

In one embodiment, the evoked response unit 172 may be a vagus evokedresponse unit, i.e., a unit configured to acquire data from the vagusnerve relating to responses evoked on a body tissue (e.g., a vagusnerve, a heart, or a brain or a region thereof) by an electricalstimulation or to acquire EEG or ECoG data. Alternatively or inaddition, the evoked response unit 172 may be a voice evoked responseunit, i.e., a unit configured to acquire data from the patient's bodyrelating to responses evoked on the vocal cords and/or other vocalapparatus by an electrical stimulation or other therapy modality. Forexample, vagus nerve stimulation may interfere with a patient's vocalcord function, e.g., by rendering the voice hoarse or husky, and anevoked response unit 172 according to this embodiment may gather andanalyze data relating to such evoked responses.

The medical device 100 may comprise a therapy titration module 160configured to titrate one or more electrical therapy parameters to atarget value according to a titration function. The titration mayinvolve decreasing the therapy parameters at certain times in responseto the occurrence of an adverse event. (As used herein, “adverse event”refers to side effects and/or other undesirable events). In someembodiments, the titration is continued until one or more of atolerable, a safe, an efficacious, and/or a target electrical parametervalue is achieved. In other words, the target dosage may be eithertolerable, efficacious or both. In some embodiments, the programmedtarget value for a titration parameter may be altered to a lower orhigher value based upon one or more of a measured level of efficacy (orlack of efficacy) or the emergence of side effects.

The titration module 160 may comprise a titration control unit 165configured to determine and implement the titration function. In someembodiments, the titration function may be determined by looking upinformation from a titration parameter module 162. In some embodiments,titration parameters for performing the titration may also be programmedinto the medical device 100 from an external programming device 250 by aphysician, and stored into memory. The titration parameters may includeone or more of the titration time period, the titration step interval,the titration step magnitude, the titration rate, and one or more otherparameters defining the titration function.

As shown in FIG. 3, in some embodiments, the therapy titration module160 may comprise a titration parameter data processing unit 330 toprocess data to implement the titration of the one or more electricaltherapy parameters; a titration algorithm unit 320 for providinginstructions relating to titrating of one or more electrical parametersof the electrical therapy signal; the titration control unit 165 toreceive data from at least one of the titration parameter dataprocessing unit 330, the titration algorithm unit 320, and the titrationparameters unit 162. Therapy titration unit 160 may further comprise anelectrical therapy parameter unit 340, operatively coupled to thetitration control unit 165, to provide one or more values of theelectrical therapy parameters to be titrated to the electrical therapymodule 150, such as one or more initial (or first) and target values forthe electrical parameters to be titrated, as well as values for otherparameter that are not intended to be titrated. In some embodiments, thetitration parameter data processing unit 330 may be configured toreceive data from a dynamic adjustment unit 168, described below. Thetitration parameter data processing unit 330 may be capable ofprocessing data to determine a titration protocol or function. Thetitration function may be defined by one or more parameters thatdetermine how the electrical therapy parameters are to be titrated tothe target value and may determine one or more titration periods,titration step intervals, titration step magnitudes, and/or titrationstep rates.

The therapy titration module 160 may further comprise a dynamicadjustment unit 168 configured to adjust one or more electricalparameters and/or titration parameters based on the feedback data from,e.g., sensors 214 and/or feedback module 180. The dynamic adjustmentunit 168 may accelerate, slow down, suspend, or resume the programmedtitration process according to body data received from the patient. Insome embodiments, the dynamic adjustment unit 168 may be used todetermine one or more of a measure of efficacy of the therapy (toidentify and/or quantify whether or not the electrical therapy isefficacious) or a side effect of the therapy, and to use such measure ofefficacy, lack of efficacy, or side effects, to cause titration controlunit 165 to accelerate, interrupt or suspend, reduce, or resume thetherapy titration process. In some embodiments, the dynamic adjustmentunit 168 may cause titration control unit 165 to adjust the one or moreelectrical therapy parameters to slow the titration of the one or moreelectrical therapy parameters to their respective target values, whilein others the titration function may be adjusted to speed up thetitration to the target value. For example, if the feedback dataindicates that the patient suffered an adverse reaction to theelectrical therapy, the dynamic adjustment unit 168 may increase thetitration step interval to slow titration of the electrical therapyparameter(s), or it may reduce one or more electrical therapy parametersbeing titrated to the most recent value not associated with an adverseeffect. Doing so may eliminate or reduce a side effect, and allow thepatient additional time to accommodate to a particular titration step.As another example, if the feedback data indicates that the patient didnot suffer an adverse reaction to the treatment and the treatment lackssufficient efficacy, the dynamic adjustment unit 168 may reduce atitration step interval to prompt a faster titration of the therapy. Inthis manner, the dynamic adjustment unit 168 and the therapy titrationmodule 160 are capable of improving safety and efficacy of therapy.

Returning to FIG. 1, the medical device 100 may comprise a feedbackmodule 180 configured to provide feedback data from the patient's body,wherein the feedback comprises at least one of body data (e.g., thatprovided by body data module 170) or a manual input from the patient(e.g., provided by patient input device 216). The feedback module 180may provide feedback relating to the efficacy of the treatment, thesafety of the treatment, one or more body reactions to the treatment,etc. The feedback module 180 may also provide external feedback receivedfrom the patient or a medical professional. Information from thefeedback module 180 may be used to adjust the titration of the therapy.

Turning now to FIG. 4, the dynamic adjustment unit 168 may also comprisea parameter magnitude adjustment unit 430, a timing module 420, anefficacy module 450, an adverse effect module 460, and a titrationoverride module 440. The parameter magnitude adjustment unit 430 may beconfigured to provide data relating to the magnitude of one or moreadjustments to be made to the value of an electrical therapy parameter.The timing module 420 may be configured for determining the timing ofone or more adjustments to be made to the value of an electrical therapyparameter to be titrated (e.g., the length of time the electricalparameter is kept at a particular value, and/or the times at which theparameter is adjusted to a next value or a previous value). Data fromthe parameter magnitude adjustment unit 430 may be utilized by thetiming module 420 to determine the timing of the adjustments to theelectrical therapy parameters.

The adverse effect module 460 (which may also be referred to as a sideeffect module) may be configured to determine at least one adverseeffect of the electrical therapy, e.g., an observation that thetreatment regimen is unsafe and/or intolerable. Data from the adverseeffect module 460 may be used by the parameter magnitude adjustment unit430 and/or timing module 420 to determine the rate of increase fortitrating one or more parameters of the electrical therapy signal. Forexample, if the adverse effect module detects that certain parametervalues of the electrical signal, at a certain point in the therapytitration process, cause an adverse event (e.g., pain, vocal problems,sudden drop in blood pressure or heart rate, etc.), the parametermagnitude adjustment unit 430 may reduce the rate of increase of anelectrical therapy parameter, maintain the current value of theparameter, or may reduce the value of the parameter, to allow theadverse event to resolve. In some embodiments, these actions may betaken for more than one electrical therapy parameter. Further, theadverse effect module 460 may correlate certain titration adjustments toadverse effects and store such data. This data may be used by medicaldevice 100 to control parameters of future titrations.

In one embodiment, the dynamic adjustment unit 168 may include anefficacy module 450 configured to determine at least one body indexcomprising a measure of efficacy of the electrical therapy. The efficacyindex may be determined based at least in part on collected body data oron reports or input from the patient. In some embodiments, the dynamicadjustment unit 168 may be configured to adjust the value of anelectrical parameter to be titrated based on the one or more efficacyindex values. Depending upon whether the efficacy module 450 indicatesthat the therapy is efficacious, not efficacious, or is indeterminate,the titration process may be modified (e.g., accelerated, interrupted orsuspended, or reversed, among others). More particularly, data from theefficacy module 450 regarding the efficacy of the electrical therapy maybe used by the parameter magnitude adjustment unit 430 to make automatedadjustments to the titration parameter(s), and/or by the timing module420 to change the timing of the adjustments to the parameter(s). As anon-limiting example, if the efficacy data indicates that the previouslyapplied treatment was not sufficiently efficacious within apredetermined time period, the electrical therapy signal may be changedby increasing the magnitude of the adjustment to be made to anelectrical therapy parameter, and/or decreasing the time period requiredbefore the next adjustment is made, in an effort to increase theelectrical therapy dosage provided to the patient. In alternativeembodiments, the efficacy module 450 may instead be a component ofanother portion of the medical device 100 rather than the dynamicadjustment unit 168.

The term “reduce” the value of the electrical parameter is used above inview of the typical situation where the titration of the electricalparameter is from a low initial value to a high target value associated(or expected to be associated) with efficacy. This is generally the casefor amplitude, pulse width, and pulse frequency. An adverse effect mayresult from a titration with too high a step magnitude or step rate, orwith a step implemented too soon (i.e., with a step interval that is tooshort) for the patient to have acclimated to a prior titration increase.In such cases, reducing the value may be appropriate to minimize orreverse the adverse effect. However, some parameters, e.g., signaloff-time, may be titrated from a high initial value to a low targetvalue associated with efficacy. In such situations, increasing the valueof the signal off-time may be appropriate to minimize or reverse theadverse effect, and to allow the patient a longer period of time tobecome habituated or acclimated to a particular titration increase.

The dynamic adjustment unit 168 may also comprise a titration overridemodule 440 for overriding the programmed titration of the electricaltherapy parameter(s). For example, based upon a signal from the adverseeffect module or an input from the patient or a healthcare provider, thetitration override module 440 may override the programmed titration. Theoverriding of the titration may include suspending a next plannedadjustment to the one or more electrical therapy parameters beingtitrated. Subsequent adjustments to the electrical therapy parameter(s)may be provided according to data generated by one or more of timingmodule 420, the parameter magnitude adjustment unit 430, efficacy module450, and adverse effect module 460. The subsequent adjustments mayinclude stopping a current titration process and implementing a defaulttitration process, ending the titration process altogether, implementinga slower titration process, implementing titration to a higher (orlower) final value, etc.

FIG. 2 shows a block diagram depiction of a medical device 100, inaccordance with one illustrative embodiment of the present invention.FIG. 2 depicts an exemplary implementation of the body data module 170described above with respect to FIG. 1. The body data module 170 mayinclude a body data memory 251 for storing and/or buffering data in thebody data module 170. The body data memory 251 may, in some embodiments,be adapted to store body data for logging or reporting purposes and/orfor future body data processing. The body data module 170 may alsoinclude one or more body data interfaces 210. The body data interface210 may provide an interface for input/output (I/O) communicationsbetween the body data module 170 and body data units/modules (e.g.,[260-270], [273-276]) via connection 280. Connection 280 may a wired orwireless connection, or a combination of the two. The connection 280 maybe a bus-like implementation or may include an individual connection(not shown) for each or some number, of the body data unit (e.g.,[260-270], [273-276]). The connection 280 may also include connectionelements as would be known to one of skill in the art having the benefitof this disclosure. The specific implementation of the connection 280does not serve to limit other aspects of various embodiments describedherein unless specifically described. In this regard, body dataacquisition units/modules 260, 270, 273, 274, 275 may also include oneor more of sensors 214 and leads 215 (FIG. 1).

In various embodiments, the body data units may include, but are notlimited to, an autonomic data acquisition unit 260, a neurologic dataacquisition unit 270, and endocrine data acquisition unit 273, ametabolic data acquisition unit 274 and/or a tissue stress marker dataacquisition unit 275. In one embodiment, the body data units may includea physical fitness determination unit 276. In one embodiment, theautonomic data acquisition unit 260 may include a heart beat dataacquisition unit 261 adapted to acquire heart sounds, EKG data, PKGdata, heart echo, apexcardiography and/or the like, a blood pressureacquisition unit 263, a respiration acquisition unit 264, a blood gasesacquisition unit 265, and/or the like. In one embodiment, the neurologicdata acquisition unit 270 may contain a kinetic unit 266 that maycomprise an accelerometer unit 267, an inclinometer unit 268, and/or thelike; the neurologic data acquisition unit 270 may also contain aresponsiveness/awareness unit 269 that may be used to determine apatient's responsiveness to testing/stimuli and/or a patient's awarenessof their surroundings. These lists are not inclusive, and the body datamodule 170 may collect additional data not listed herein, that wouldbecome apparent to one of skill in the art having the benefit of thisdisclosure. The body data acquisition units ([260-270], [273-276]) maybe adapted to collect, acquire, receive and/or transmit heart beat data,EKG data, PKG data, heart echo, apexcardiography, heart sound data,blood pressure data, respiration data, blood gases data, bodyacceleration data, body incline data and/or the like.

The body data interface(s) 210 may include various amplifier(s) 220, oneor more A/D converters 230 and/or one or more buffers 240 or othermemory (not shown). In one embodiment, the amplifier(s) 220 may beadapted to boost incoming and/or outgoing signal strengths for signalssuch as those to/from any body data units/modules (e.g., ([260-270],[273-276]) or signals to/from other units/modules of the IMD 200. TheA/D converter(s) 230 may be adapted to convert analog input signals frombody data unit(s)/module(s) (e.g., ([260-270], [273-276]) into a digitalsignal format for processing by controller 210 (and/or processor 215).Such analog signals may include, but is not limited to, heart beat data,EKG data, PKG data, heart echo, apexcardiography, heart sound data,blood pressure data, respiration data, blood gases data, bodyacceleration data, body incline data and/or the like. A converted signalmay also be stored in a buffer(s) 240, a body data memory 251, or someother memory internal to the IMD 200 (e.g., memory 217) or external tothe IMD 100 (e.g., patient input device 216 or programmer 250). Thebuffer(s) 240 may be adapted to buffer and/or store signals received bythe body data module 170 as well as signals to be transmitted by thebody data module 170. In various embodiments, the buffer(s) 240 may alsobe adapted to buffer and/or store signals in the body data module 170 asthese signals are transmitted between components of the body data module170.

FIG. 5 depicts a stylized depiction of one example of a titration of anelectrical therapy, according to some embodiments herein. In oneembodiment, the illustration in FIG. 5 may represent a titration of afirst electrical therapy parameter, e.g., the current amplitude of thetherapy signal. In alternative embodiments, the illustration of FIG. 5may represent a titration of a plurality of parameters, e.g., acomposite representation of amplitude and pulse width or frequency.Additional but different figures, having different timing and magnitudefor the adjustments, could be provided for a second, third, fourth,etc., parameter to be titrated. Those skilled in the art having benefitof the present disclosure would appreciate that the general principlesof FIG. 5 are applicable to any electrical parameter that may be part ofa titration of an electrical therapy of a patient by adjusting theparameter from a first value to a target value.

Starting from a first or initial magnitude shown in FIG. 5, the firstelectrical therapy parameter may be increased by a titration stepmagnitude (dashed line shown in FIG. 5 as being the same for each stepbut which may be different in alternative embodiments) at each of aplurality of titration step intervals (also depicted as uniform in FIG.5 but which may be different in alternative embodiments. The period fromthe initial time (when the therapy is started) to the time at which thetarget value is reached is the titration time period. From the initialtime to 1^(st) step, the electrical therapy parameter remains at thefirst value to allow the patient's body to be acclimated to the therapysignal at the first value. At the first step, the first parameter valueis increased to a second, higher value (e.g., from 0.1 to 0.2 mA), andit remains at that value for the titration step interval, at the lapseof which the first parameter value is then increased (at the 2^(nd)step) to a 3rd, still higher value. The first parameter remains at the3rd value for another titration step interval, at which time (the 3^(rd)step), when the value is raised to a 4^(th) value. After the lapse ofanother titration step interval, the first parameter is then increased(at the 4^(th) step) to the target value. The representative processillustrated may be made in a greater number of steps with smallertitration step magnitudes to improve the patient's ability to tolerateeach step. The stepwise process is repeated until the target value ofthe first parameter is reached. The time to target value may bedetermined by the timing module 420 (FIG. 4) of the dynamic adjustmentmodule 170.

FIG. 5 also shows the titration rate on two timescales, e.g., a globaltime scale (dotted line), comparable in value to the sum of thetitration step magnitudes divided by the time to target level, and localtime scales (dashed and dashed-dotted lines), indicating alternativeapproaches to bringing the amplitude up to the level of a next step.

The patient's tolerance for an increase in a titrated parameter may varydepending on the patient's state, e.g., the patient's level ofconsciousness, level of attention, mood, general health, gender, age,etc. Changes in the titration process may be made accordingly. Forexample, if the patient is more tolerant of the increase at night, acurrent setting may be increased at night (e.g., while the patient isasleep) from a lower amplitude to a higher amplitude. Upon awakening,the amplitude may be maintained at the higher amplitude or reduced to anintermediate value if the patient does not tolerate the higher amplitudewhen awake. In this manner, the titrating function may accelerate thepatient's accommodation to the higher amplitude and/or accelerate theoverall titration process.

FIG. 6 illustrates a stylized depiction of one example of a dynamicadjustment of a titration function, according to some embodiments.Again, by way of example, the depicted value along the y-axis of FIG. 6is the first electrical therapy parameter, e.g., current amplitude. Thegeneral principles illustrated, however, are applicable to anyelectrical therapy parameter that may be titrated as part of a therapytitration to an efficacious dosage. In this example, an adverse effect(not shown) is determined to occur sometime after titrating up to the3^(rd) step. As shown, the dynamic adjustment comprises reducing thevalue of the first parameter, e.g., current amplitude, to the last knowntolerable value (e.g., the value of the 2^(nd) step), lengthening of theduration of the current tolerable/safe magnitude before the firstparameter is titrated to the next higher magnitude. In one embodiment,subsequent steps may be initiated at the originally programmed stepmagnitude, as illustrated by the series of steps leading to the targetvalue (dashed line), while in alternative embodiments, the dynamicadjustment may also or alternatively comprise decreasing the stepmagnitude to be applied at future titration steps, as shown by theadjusted steps having a smaller magnitude than the earlier (1^(st),2^(nd) and 3^(rd)) step magnitudes (dotted line).

In embodiments having a reduced step magnitude, a new (greater)titration time period for reaching the target value may be determined.That is, upon detection of an adverse event, the titration stepmagnitude may be reduced for future titration steps resulting in alonger titration time period necessary to reach the target value for theelectrical therapy parameter(s) being titrated. In this manner, a morecomfortable and/or safer titration process may be provided to thepatient.

FIG. 7 illustrates a flowchart representation of a method 700 forperforming an automated titration of one or more electrical therapyparameters in accordance with some embodiments herein. Parametersdefining an electrical therapy may be programmed (block 710) into amedical device based upon at least one target value for an electricalparameter to be titrated (e.g., an electrical therapy that the patientcannot immediately tolerate at the dosage associated with the targetvalue). The therapy regimen may be configured to treat one or more ofseveral diseases, such as epilepsy, depression, pain, congestive heartfailure, traumatic brain injury, or obesity.

Programming at 710 may include providing first value(s) and targetvalue(s) for at least one parameter.

One or more titration parameters characterizing the titration of the oneor more electrical therapy parameters being titrated may be programmedinto the medical device (block 720). The electrical therapy may beimplemented with the electrical therapy parameters to be titrated havingtheir first or initial values (block 730). Thereafter, the electricaltherapy may be automatically titrated (block 740) based on theprogrammed target value(s) of the electrical parameter(s), the titrationparameters, and a titration function. The titration function may includevarious patterns for adjusting the electrical therapy parameter(s),e.g., uniform titration magnitude steps and titration step intervals, ornon-uniform adjustments (e.g., according to a parabolic function, ahigher-order polynomial, etc.).

In some embodiments, the method 700 may further comprise sending amessage to the patient and/or a caregiver or healthcare provided aphysician when the target value is reached, or when a change to theprogrammed titration has occurred, or when a side effect has beendetected.

FIG. 8 illustrates a flowchart depiction of automatically titrating theelectrical therapy based upon the titration parameters and the titrationfunction (block 740 of FIG. 7), in accordance with some embodimentsherein. At block 810, the medical device 100 may deliver the therapy atthe first (initial) values for the electrical therapy parametersprogrammed into the medical device.

As the therapy is delivered, logic in the MD 100 determines whether ornot the titration step interval has elapsed (block 820). If so, theelectrical therapy parameter(s) to be titrated are adjusted by thetitration step magnitude (block 830).

In one embodiment, titration logic in the MD 100 determines whether ornot an adverse effect has occurred (block 840). If no adverse event hasoccurred, the logic thereafter checks to determine if the next titrationstep interval has elapsed (block 850). If the titration step intervalhas not elapsed, the logic continues to check for adverse effects (block840), and if the titration step interval has elapsed, the logic checksto determine if current value of the electrical signal parameter is thefinal value (block 860). If the current value is the final value, MD 100continues to operate the therapy with the parameter at the target value(block 870), while if the final titration value has not been reached,the logic again adjusts the electrical therapy by the titration stepmagnitude (830).

If at any point after an adjustment is made (block 830) an adverseeffect occurs (block 840), the value of the electrical therapy parameteris reduced to a prior tolerable value (block 880), e.g., a highestpreviously tolerable amplitude. In some embodiments, changes to one ormore of the titration step magnitude and the titration step interval mayalso be made as part of block 880. In alternative embodiments, thetherapy may be suspended rather than continued at a reduced stimulationdosage. After the reduction of the electrical therapy parameter to alower value (with or without changes to the step magnitude and/orinterval), the logic then checks to determine if the titration stepinterval has elapsed (either as originally programmed or as modified) atstep 890. If the interval has elapsed, the electrical therapy parameteris adjusted by the titration step magnitude at step 830.

The indications of an adverse effect or event (840) may be based on oneor more body indices derived from a body signal. Exemplary body indicesinclude one or more of the patient's heart rate, heart rate variability,blood oxygen saturation, respiratory rate, blood oxygen saturationvariability, respiratory rate variability, discomfort, shortness ofbreath, or vocal cord function. Unacceptable changes indicative of alack of patient tolerance may be used to indicate the occurrence of anadverse effect. Alternatively or in addition, a manual input from thepatient or another external source, such as a medical professional, maybe used to indicate an adverse effect. Exemplary manual inputs includebut are not limited to tap sensor inputs, magnetic sensor inputs,manipulation of one or more physical or virtual keys on a handhelddevice, etc.

In some embodiments, the adverse event indication may include a severityof the adverse effect, or to the rate of occurrence of an effect that ata low rate would not be an adverse effect. When adverse events occur,the magnitude of the reduction of the electrical signal parameter and/orchanges to the titration step interval and step magnitude (block 880)may be based on the type, severity and/or rate of the adverse effect.

In some embodiments, if no adverse effect is determined at block 840 tohave occurred, then the current and/or a future second period can beshortened, i.e., the titration of the parameter may take place morerapidly than originally programmed if there are no significant adverseeffects.

Turning to FIG. 9, a simplified flowchart diagram for performing atitration process in accordance with some embodiments herein isillustrated. A dosage for providing a therapy may be determined, andbased upon the dosage, a titration regimen may be initiated (block 910).In some embodiments, the titration regimen is based upon the dosageand/or one or more specific characteristics of the patient, e.g.,patient tolerance level.

Upon performing one or more upward titration steps, one or more bodydata may be received and analyzed to determine whether there exists anadverse effect (block 930). In other embodiments, an external source mayprovide the medical device 100 an indication of an adverse effect. Forexample, the patient may provide a manual input that is indicative of anadverse effect. In other embodiment, the medical device 100 may receivea signal from an external device, indicating an adverse effect.

Upon a determination that no adverse effect has been found (block 930),the medical device may determine whether the final dosage has beenreached (block 940). If the final dosage has been reached, the medicaldevice may stop the titration process and save the titration parameters(block 950). Upon a determination that the final dosage has not beenreached (block 940), the medical device may continue the titrationprocess (block 920), e.g., by implementing a next titration step uponthe passage of a titration step interval. The process may continue aspreviously discussed (e.g., by returning to block 930).

If the medical device 100 determines that at least one adverse effecthas been found (block 930), the medical device 100 may implement amodification of the titration regimen (block 960). This modification maybe automatically performed based upon the type of adverse effectsdetected. Alternatively, or in addition, manual input from a person, orautomated input based upon body data, may also affect modification ofthe titration regimen.

Upon implementing the modified titration regimen, the medical device 100may again determine whether an adverse effect has been found (block970). If an adverse effect is found, the medical device 100 may againimplement a modification of the titration regimen (as indicated by thepath from block 970 to 960). If an adverse effect is not found (block970) and the final dosage has been reached (block 980), the titrationprocess is terminated and the titration parameters are saved (block950). If the final dosage has not been reached (block 980), the medicaldevice 100 may continue the titration process, moving the titration inthe direction of the final dosage (see path from block 980 to 920). Inthis manner, an automated and/or manual implementation of a titrationregimen, moving upwardly towards the therapy dosage, is implementedwhile reducing the risk of adverse effects.

Turning now to FIG. 10, a flowchart diagram for a method of implementinga titration interrupt and/or a multi-titration process, in accordancewith some embodiments is illustrated. Upon determining a dosage fortherapeutic treatment stimulation for a disease such as epilepsy, anon-event-specific state titration process may be initiated (block1010). The non-event-specific state titration process is performed toautomatically initiate a treatment regimen, to gradually reach a fulldosage regimen to treat a condition (e.g., epilepsy). Thenon-event-specific state titration is performed at pre-programmed timesand in pre-programmed steps independent of the occurrence of seizures,(e.g., open-loop process). That is, in some embodiments, thenon-event-specific state titration process may be not responsive to aparticular epileptic event. In one embodiment, the non-event-specificstate titration process may be implemented in the manner described inFIG. 9.

Continuing referring to FIG. 10, the medical device 100 may continuouslycheck to determine whether an epileptic event (e.g., a seizure, a fallassociated with a seizure, an accident associated with a seizure, etc.)is detected (block 1020). If no epileptic events are detected, thenon-event-specific state titration process is continued (block 1030). Ifand when an epileptic seizure is detected, the non-event-specific statetitration process may be temporarily interrupted (block 1040). Uponinterrupting the non-event-specific state titration process, in oneembodiment, the medical device 100 may implement an event-specifictherapy (block 1050) (e.g., closed-loop). The event-specific therapy maybe a specific therapy regimen that is directed to treat the specifictype of event (e.g., seizure) that is detected. For example a 1sttherapy signal may be provided for a clinical seizure, while 2nd therapymay be provided for a sub-clinical seizure. In other embodiment, a 1sttherapy signal may be provided for a generalized seizure, while a 2ndtherapy signal may be provided for a partial seizure. In yet otherembodiments, other distinctions for seizures (e.g., simple partial orcomplex partial or secondarily generalized seizure etc.) may be used toimplement specific therapy signals tailored to address thosedistinctions. In some embodiment, a look-up function may be performed toselect the various parameters (e.g., frequency, pulse-train parameters,pulse-width, inter-pulse interval, amplitude, etc.) relating to thetherapy signal. The event-specific therapy/titration process may beclosed-loop process, specific to the treatment of the epileptic event,wherein this process terminates with the epileptic event.

In an alternative embodiment, upon interrupting the non-event-specificstate titration process (block 1040), an event-specific titrationprocess may be implemented (block 1060). The event-specific titrationprocess may provide for determining a dosage to treat the specificepileptic event that has been detected, and initiate a treatment regimenusing parameter settings that are increased to a full-dosage setting totreat the epileptic event. Upon implementing the event-specific (e.g.,closed-loop) titration process, the medical device 100 may thenimplement an event-specific therapy based upon the event-specifictitration. In one embodiment, the time-periods relating to the step-wiseincreases in one or more parameters associated with the event-specifictitration process are equal to or larger than those relating to thenon-event-specific state titration process. The event-specifictherapy/titration process may be closed-loop process, specific to thetreatment of the detected epileptic event, wherein this processterminates with the epileptic event.

Upon performing either of the two processes of blocks 1040 and 1060(event-specific therapy or event-specific titration), the medical device100 may determine whether the epileptic event had concluded orsufficiently subsided (block 1070). Upon a determination the epilepticevent has not sufficiently subsided, the event-specific therapy orevent-specific titration is continued (block 1080). Upon a determinationthe epileptic event has concluded or has sufficiently subsided, themedical device 100 may revert back to the non-event-specific statetitration process (block 1090).

In some embodiments, the present disclosure may relate to a method ofproviding a bringing an electrical stimulation regimen administered by amedical device to a target dosage, comprising programing a therapyregimen based upon at least one target electrical parameter; programmingone or more titration parameters for titrating to the target electricalparameter; initiating the electrical therapy at the programmed initialvalues; receiving a body signal after initiating the therapy at theprogrammed initial values; determining whether there is an adverseeffect associated with the therapy, based upon the body signal;adjusting one or more titration parameters to yield an adjustedtitration, in response to a determining that there is an adverse effectassociated with the therapy; implementing the adjusted titration, andtitrating the at least one target electrical parameter according to theadjusted titration.

Receiving the body signal may comprise receiving at least one ofautonomic data, neurological data, endocrine data, metabolic data,tissue stress marker data, responsiveness data, or physical fitnessdata.

Adjusting may comprise returning the electrical parameter value to aprior value. The adjusted therapy may be safe, efficacious, and/ortolerable.

This method may further comprise alerting a physician, in response to acardiac or respiratory adverse effect.

This method may further comprise determining an efficacy of the adjustedtherapy. This method may further comprise stopping the titration processand notifying a physician, in response to the adjusted therapy beingefficacious before the target parameter is reached.

In some embodiments, the target electrical parameter may be selectedfrom an amplitude, a pulse width, a pulse frequency, a signal on-time, awaveform, a level or degree of charge balance in a pulse, a polarity, asignal off-time, or two or more thereof. For example, adjusting thetherapy may comprise at least one of reducing an electrical currentamplitude of the electrical parameter, or determining a modifiedtitration function.

In some embodiments, increasing the electrical parameter value may beperformed during states in which taking said step is most comfortable orsafe. For a therapy such as vagus nerve stimulation that may causethroat discomfort or coughing, increasing the electrical parameter maybe performed while the patient is asleep when the discomfort or painthresholds are higher than during wakefulness. In some embodiments, thetitration may comprise detecting a patient state, where the patientstate is one or more of sleeping, awake, resting awake, sitting andawake, active and awake, and exercising. Detecting whether the patientis sleeping may further comprise detecting a sleep state of the patientselected from stage 1, stage 2, stage 3, stage 4, and REM sleep, lightsleep, and deep sleep. In some embodiments, where the electrical therapymay use bradycardia, increasing the electrical parameter value may takeplace only while the patient is awake to minimize the risk of notdetecting symptoms associated with the slowing down of the patient'sheart rate.

The electrical stimulation regimen of this method may be configured totreat epilepsy, depression, pain, congestive heart failure, traumaticbrain injury, or obesity.

In any of the automatic titration methods described herein, thetitration may be suspended at any step upon the detection of an acutemanifestation of the patient's illness, e.g., a seizure if the patientsuffers epilepsy, and an alternative, closed-loop therapy to treat theacute manifestation may be implemented. (The acute therapy may involve asecond titration process. Further, the second titration process may beimplemented by a function that uses as input(s) information regardingthe first titration process). Upon termination of the acutemanifestation, the titration may be resumed, typically at the step atwhich it was suspended. In some embodiments, however, the titration maybe resumed at a higher or lower step.

In some embodiments, a method is provided for performing an interruptionof a non-event specific titration process (e.g., open-loop) performed byan implanted medical device, comprising: a) programming the medicaldevice to provide an electrical therapy, wherein the programmedelectrical therapy comprises a first target value for a first electricaltherapy parameter defining the electrical therapy; b) programming atleast one titration parameter for automatically adjusting the firstelectrical therapy parameter from a first value to the first targetvalue over a titration time period of at least two days, wherein the atleast one titration parameter is selected from the titration timeperiod, a titration step interval, a titration step magnitude, and atitration step rate; initiating the electrical therapy, wherein thefirst electrical therapy parameter comprises said first value; c)automatically titrating the electrical therapy by making a plurality ofadjustments to the value of the first electrical therapy parameter,whereby the first electrical therapy parameter is changed from the firstvalue to a second target value according to a titration function; d)detecting an epileptic event; e) interrupting the open-loop titratingprocess in response to detecting an epileptic event; f) providing anevent-specific (e.g., closed-loop) therapy; and g) reverting back to thenon-event specific titration process in response to a determination thatthe epileptic event has concluded.

In other embodiments, a method is provided for performing aninterruption of a non-event specific titration process performed by animplanted medical device, comprising: a) performing a non-event specifictitration process; b) detecting an epileptic event; c) interrupting thenon-event specific titration process in response to detection theepileptic event; d) implementing an event-specific titration process fordelivering a therapy in response the detection of the epileptic event;and e) reverting back to the non-event specific titration process inresponse to a determination that the epileptic event has concluded.

In yet another embodiment, a method is provided for modifying atitration process for providing a therapy by a medical device (fullyimplanted, partially implanted or external to the patient) comprising:a) initiating a titration process to treat a chronic condition, whereinthe titration process includes programming at least one titrationparameter for automatically adjusting an electrical therapy parameterfrom a first value to the first target value over a titration timeperiod; b) determining whether an adverse effect resulting from thetitration has been found; c) modifying at least one parameter associatedwith the titration process; and d) implementing a modified titrationprocess. In some embodiments, the titration process and/or the modifiedtitration process is continued upon determining that a final dosage ofthe therapy had been reached.

The methods described above may be implemented by the medical device 100and/or the medical device system 150. The methods described above may begoverned by instructions that are stored in a non-transitory computerreadable storage medium and that are executed by, e.g., a processor 217of the medical device 100.

The methods depicted in FIGS. 7-10 and/or described above may begoverned by instructions that are stored in a non-transitory computerreadable storage medium and that are executed by, e.g., a processor 217of the medical device 100. Each of the operations shown in FIGS. 7-10and/or described above may correspond to instructions stored in anon-transitory computer memory or computer readable storage medium. Invarious embodiments, the non-transitory computer readable storage mediumincludes a magnetic or optical disk storage device, solid state storagedevices such as flash memory, or other non-volatile memory device ordevices. The computer readable instructions stored on the non-transitorycomputer readable storage medium may be in source code, assemblylanguage code, object code, or other instruction format that isinterpreted and/or executable by one or more processors.

What is claimed:
 1. A method of treating a medical condition of apatient via an implantable medical device comprising: initiating via oneor more processors of the implantable medical device a titration periodfor a first therapy with a first treatment period based on an inputobtained from the patient, the first therapy including an electricalstimulation with one or more parameters; initiating a modificationprocedure of one or more values associated with the one or moreparameters during the titration period; and initiating the first therapyfor the first treatment period based on one or more parameters beingtolerated by the patient or reaching one or more target values.
 2. Themethod of claim 1, further comprising initiating a second titrationperiod for a second therapy with a second treatment period.
 3. Themethod of claim 2, further comprising initiating a third therapy basedon an acute event detection.
 4. The method of claim 1, furthercomprising initiating a third therapy based on an acute event detection.5. The method of claim 1, wherein one or more changes in the one or morevalues associated with the one or more parameters during the titrationperiod do not cause an adverse effect.
 6. The method of claim 1, whereinthe input obtained from the patient occurs via a magnetic sensor input.7. The method of claim 1, wherein the one or more processors of theimplantable medical device modifies at least one of the titration periodand the modification procedure of one or more values associated with theone or more parameters based on at least one of a patient's age, apatient's level of consciousness, a patient's level of attention, apatient's health status, a patient's gender, a severity of a disorderbeing treated, a patient's tolerance to one or more adverse events, anda patient's tolerance to pain.
 8. The method of claim 1, furthercomprising: initiating via one or more processors of the implantablemedical device a second titration period for a second therapy with asecond treatment period, the second therapy including a secondelectrical stimulation with a second set of parameters; initiating asecond modification procedure based on the second set of parameters witha second set of target values; and initiating the second therapy for thesecond treatment period based on at least one parameter of the secondset of parameters being tolerated by the patient or reaching at leastone of the second set of target values.
 9. The method of claim 1,wherein the one or more processors of the implantable medical devicemodifies at least one of the titration period and the modificationprocedure of one or more values associated with the one or moreparameters based on at least one of an emergence of one or more sideeffects, a level of efficacy, and an event detection.
 10. The method ofclaim 1, wherein the event detection is an acute event detection. 11.The method of claim 1, further comprising acquiring data for at leastone of a status report, a historical report, and an alert andtransmitting the acquired data or the alert to an external device. 12.The method of claim 1, wherein the one or more processors modifies atleast one of the titration period and the modification procedure of oneor more values associated with the one or more parameters based on thepatient being asleep.
 13. An implantable medical device comprising: oneor more processors configured to initiate a titration period for a firsttherapy with a first treatment period based on an input obtained from apatient, the first therapy including an electrical stimulation with oneor more parameters; the one or more processors further configured toinitiate a modification procedure of one or more values associated withthe one or more parameters during the titration period and to initiatethe first therapy for the first treatment period based on one or moreparameters being tolerated by the patient or reaching one or more targetvalues.
 14. The implantable medical device of claim 13, wherein themodification procedure of the one or more parameters is a gradualfunction during the titration period or the titration period isadjusted.
 15. The implantable medical device of claim 13, wherein theinput obtained from the patient occurs via a magnetic sensor input. 16.The implantable medical device of claim 15, wherein the one or moreprocessors of the implantable medical device are configured to modify atleast one of the titration period and the modification procedure of oneor more values associated with the one or more parameters based ondetecting a sleep state of the patient which includes at least one of astage one, a stage two, a stage three, a stage four, a REM sleep, alight sleep, and a deep sleep.
 17. The implantable medical device ofclaim 13, wherein the one or more processors of the implantable medicaldevice are configured to modify at least one of the titration period andthe modification procedure of one or more values associated with the oneor more parameters based on detecting a sleep state of the patient whichincludes at least one of a stage one, a stage two, a stage three, astage four, a REM sleep, a light sleep, and a deep sleep.
 18. Theimplantable medical device of claim 13, wherein the one or moreprocessors of the implantable medical device are configured to modify atleast one of the titration period and the modification procedure of oneor more values associated with the one or more parameters based on atleast one of an emergence of one or more side effects, a level ofefficacy, and an event detection.
 19. The implantable medical device ofclaim 13, wherein the one or more processors of the implantable r edicaldevice are configured to modify the one or more values on the one ormore parameters to a prior tolerable value based on a first statedetermination which is an emergence of one or more side effects, the oneor more processors of the implantable medical device are configured tomodify the one or more values on the one or more parameters based on asecond state determination which is at least one of a level of efficacyand an event detection.
 20. The implantable medical device of claim 13,further including a transceiver configured to transmit at least one of astatus report, a historical report, and an alert to an external device.21. The implantable medical device of claim 13, further including atransceiver configured to receive an indication of an adverse effect.22. The implantable medical device of claim 13, further including atransceiver configured to receive an indication of an adverse effectfrom an external source.
 23. A method of treating a medical condition ofa patient via an implantable medical device comprising: initiating viaone or more processors of the implantable medical device a titrationperiod for a therapy, the therapy including at least an electricalstimulation with one or more parameters; setting one or more parametervalues to air initial electrical stimulation parameter level where theinitial electrical stimulation parameter level is tolerable to thepatient; increasing the one or more parameter values to an efficaciouslevel based on a lack of side effects being produced by the initialelectrical stimulation parameter level; modifying at least one of theone or more parameter values and a rate of change of the one or moreparameter values based on at least one of the one or more paravalues andthe rate of change of the one or more parameter values generating anintolerable state for the patient; and discontinuing the modificationstep based on reaching an efficacy level and a patient tolerable level.24. The method of claim 23, wherein the one or more processors of theimplantable medical device modifies the titration period based on atleast one of a patient's age, a patient's level of consciousness, apatient's level of attention, a patient's health status, a patient'sgender, a severity of a disorder being treated, a patient's tolerance toone or more adverse events, and a patient's tolerance to pain.
 25. Themethod of claim 23, wherein the one or more processors of theimplantable medical device modifies the rate of change of the one ormore parametervalues based on at least one of a patient's age, apatient's level of consciousness, a patient's level of attention, apatient's health status, a patient's gender, a severity of a disorderbeing treated, a patient's tolerance to one or more adverse events, anda patient's tolerance to pain.
 26. The method of claim 23, furthercomprising acquiring data for at least one of a status report, ahistorical report, and an alert and transmitting the acquired data orthe alert to an external device.
 27. The method of claim 23, wherein theone or more processors modifies at least one of the titration period andthe rate of change of the one or more parameter values based on thepatient being asleep.
 28. The method of claim 23, wherein the one ormore processors of the implantable medical device are configured tomodify at least one of the titration period and the rate of change ofthe one or more parameter values based on detecting a sleep state of thepatient which includes at least one of a stage one, a stage two, a stagethree, a stage four, a REM sleep, a light sleep, and a deep sleep. 29.The method of claim 23, wherein the intolerable state is determinedbased on at least one of an input from the patient and biologicalsignals from the patient.
 30. The method of claim 29, wherein thebiological signals are recorded.